الملخص الإنجليزي
Breast cancer (BC) is a common form of disease affecting 25% of women worldwide. In Oman, BC is the most common cancer among women, representing approximately 17% of all cancers in women. Surprisingly, BC affects a relatively younger population (25-40) years and is more likely to be a more aggressive subtype and generally presented at an advanced stage (Stage III or IV). These breast tumors fail to show any significant and functional relevant mutations in BRCA1. The objective of the present study was to determine the most common BRIP/ mutations,
Methods: DNA samples extracted from breast tumors of Omani patients (80 including controls) were examined by PCR and the entire coding sequence of the BRIP1 gene was screened for mutation using sequence analysis. The relationship between clinicopathological characteristics and BC was studied using Statistical Package for the Social Sciences version 23(SPSS version23).
Results: Screening for mutations by direct sequencing identified two major functional variants in BRIP) at a significantly high rate, the 27557>C (80%), found in the BRCA binding domain and C-141-646>A (70%) detected in the promoter region, along with two previously identified polymorphisms, c.2637G>A and c.34110>T, within BRCA1 binding domain. Upon statistical analysis, we found the two mutations 27557>C & c.-141 - 64G>A, to be associated with the presence of breast cancer at a highly significant level (p<0.005).
These were also found to be associated with the consumption of oral contraceptive pills (p<0.05) and early onset of the breast cancer (p<0.05).
Conclusion: The identified mutations can be associated with instability and functional impairment of the encoded protein and provide further evidence for a functional role of BRIPI in breast cancer.
